Wound healing is a complex, highly-coordinated process that begins and ends with tissue remodeling. The extracellular matrix and its associated growth regulatory substances play a pivotal role in dynamically and reciprocally regulating the cellular response and wound healing. Initially believed to be solely important as an early component of the provisional, blood-borne matrix, the enzymes and structural macromolecules of the extracellular matrix cooperate with cytokines and growth factors, yielding a dynamic that orchestrates healing (1-7).
Wound healing and chemotactic properties of peptides obtained by collagenase-digestion of collagen have been known since the late 1970s. See, Postlethwaite et al., Proceedings of the National Academy of Science, 75:871-875 (1978).
Under normal circumstances, the process of acute wound healing can be broken down into three phases. An initial inflammatory phase, which is followed by robust tissue remodeling and proliferation (the proliferative phase), is succeeded by a “maturational phase” wherein re-epithelialization, dermal angiogenesis and wound closure ensues. Re-epithelialization involves the migration and proliferation of epithelial tissue, primarily keratinocytes. Angiogenesis is the growth of new blood vessels from pre-existing conduits, and is regulated by a panoply of soluble cytokines including growth factor polypeptides, as well as cell-cell and cell-matrix interactions. Chronic wounds exhibit a different healing profile from normal acute wounds in that they generally remain in an inflamed state for protracted periods of time. Non-healing wounds can most commonly be observed amongst people with diabetes, venous stasis disease, and in those patients who are immobilized.